The DOI matches its Crossref record; 111 of the 111 references it cites were found in a registry or an index.
Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets
Open accessAbstract
Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis , 121 trans ). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.
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Cites
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Cited by
Suhre, K., Venkataraman, G. R., Guturu, H., Halama, A., Stephan, N., Thareja, G., Sarwath, H., Motamedchaboki, K., Donovan, M. K. R., Siddiqui, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45233-y · Cited by 57
Wang, Q. S., Hasegawa, T., Namkoong, H., Saiki, R., Edahiro, R., Sonehara, K., Tanaka, H., Azekawa, S., Chubachi, S., Takahashi, Y., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01896-3 · Cited by 43
Suhre, K., Chen, Q., Halama, A., Mendez, K., Dahlin, A., Stephan, N., Thareja, G., Sarwath, H., Guturu, H., Dwaraka, V. B., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02413-w · Cited by 14
Metadata
- Authors
- Zhao, J. H., Stacey, D., Eriksson, N., Macdonald-Dunlop, E., Hedman, Å. K., Kalnapenkis, A., Enroth, S., Cozzetto, D., Digby-Bell, J., Marten, J., Folkersen, L., Herder, C., Jonsson, L., Bergen, S. E., Gieger, C., Needham, E. J., Surendran, P., Estonian Biobank Research Team, Metspalu, A., Milani, L., Mägi, R., Nelis, M., Hudjašov, G., Paul, D. S., Polasek, O., Thorand, B., Grallert, H., Roden, M., Võsa, U., Esko, T., Hayward, C., Johansson, Å., Gyllensten, U., Powell, N., Hansson, O., Mattsson-Carlgren, N., Joshi, P. K., Danesh, J., Padyukov, L., Klareskog, L., Landén, M., Wilson, J. F., Siegbahn, A., Wallentin, L., Mälarstig, A., Butterworth, A. S., & Peters, J. E.
- Venue
- Nature Immunology
- Published
- 2023-08-10
- Volume
- 24
- Issue
- 9
- Pages
- 1540-1551
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W4385740978
- Cited by
- 747
- References
- 111
- FWCI
- 110.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zhao, J. H., Stacey, D., Eriksson, N., Macdonald-Dunlop, E., Hedman, Å. K., Kalnapenkis, A., Enroth, S., Cozzetto, D., Digby-Bell, J., Marten, J., Folkersen, L., Herder, C., Jonsson, L., Bergen, S. E., Gieger, C., Needham, E. J., Surendran, P., Estonian Biobank Research Team, Metspalu, A., . . . Peters, J. E. (2023). Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets. Nature Immunology. https://doi.org/10.1038/s41590-023-01588-w
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
